Controversy exists among scientists, policy makers, and the public/media regarding health risks and benefits of fish intake in adults. Evidence indicates that long-chain n-3 fatty acids (n-3 FA) reduce risk of cardiovascular disease (CVD). Conversely, exposure to methylmercury (MeHg) present in some fish species may increase CVD risk. Fish are also a major source of selenium (Se), a trace element that may protect against MeHg toxicity. Thus, simultaneous consideration of CVD risks and benefits of n-3 FA, MeHg, and Se is necessary to allow informed decision-making by individuals and policy makers. Unfortunately, prior analyses of CVD effects of fish intake have generally focused either on risks of MeHg or benefits of n-3 FA (or, more rarely, of Se), rather than investigating their joint impact on CVD health. Accurate quantitative assessment of total effects of MeHg, Se, and n-3 FA would require comparable and objective biomarker assessments of each exposure in the same population, with adequate numbers of prospectively ascertained CVD endpoints and standardized covariate evaluation to minimize bias and imprecision. This Revision will dramatically accelerate the tempo of scientific research by adding to the parent grant objective biomarkers of n-3 FA levels and personnel/staff support to (1) prospectively investigate, using comparable and objective methods, the effects of n-3 FA, MeHg, and Se on CVD endpoints and (2) derive an evidence-based risk-assessment framework to quantify CVD effects of consuming specific fish species containing varying n-3 FA, MeHg, and Se. This research will overcome, for the first time, the present major limitations in the field. This Revision also will directly stimulate the U.S. economy by providing substantial job creation, including several new positions, as well as increased hours and retention of current staff and procurement of additional necessary equipment. PUBLIC HEALTH RELEVANCE: The research questions are important, novel, and timely for both science and public health policy. In addition to informing CVD risks and benefits of fish consumption and stimulating the US economy, the risk-assessment framework developed during this work will also inform future risk-benefit modeling of other key health outcomes affected by fish consumption, such as brain development in utero and infancy.